Eukaryotic ribosome peptidyl transferase center (PTC)

The eukaryotic ribosome peptidyl transferase center (PTC) is the catalytic heart of the 60S ribosomal subunit, responsible for forming peptide bonds during protein synthesis (Noller, 2012). While traditionally viewed as a constitutive enzyme, recent research has identified the PTC as a site for context-dependent regulation, where specific nascent polypeptide sequences interact with the PTC and the ribosomal exit tunnel to modulate translation rates (Li et al., 2019). This mechanism has been exploited by small molecules like PF-06446846, which selectively stalls the ribosome during the translation of specific proteins such as PCSK9 (Lintner et al., 2017). By targeting the PTC in a sequence-specific manner, these drugs offer a novel approach to therapeutic intervention, allowing for the modulation of previously undruggable targets by preventing their synthesis at the source. However, ensuring high specificity to avoid global translation inhibition remains a primary challenge in developing drugs for this target.

Other names

60S ribosomal subunit peptidyl transferase centerRibosomal PTCLarge ribosomal subunit active site28S rRNA catalytic centerPeptidyltransferase

Sequence-specific or general inhibition of peptide bond formation and translation elongation by binding to the peptidyl transferase center and inducing ribosome stalling through interactions with the nascent polypeptide chain (Lintner et al., 2017; Li et al., 2019).